More active analgesic combinations are in constant demand because they offer the attractive possibility of relieving pain with reduced dosages thereby diminishing the expected side effects and toxicity that would result from the otherwise required higher dosages.
U.S. Pat. No. 3,393,197, issued to Pachter and Matossian on July 16, 1968, discloses N-substituted-14-hydroxydihydronormorphines, including the N-cyclo-butylmethyl derivative, commonly called nalbuphine: ##STR1## Pachter and Matossian and others, such as H. W. Elliott, et al., J. Med. (Basel), 1, 74-89 (1970); H. Blumberg, et al., Pharmacologist, 10, 189 (Fall 1968); P. Roberts, Drugs of the Future, 2, 613-5 (1977), disclose the use of nalbuphine as an analgesic for the control of moderate to severe pain.
U.S. Pat. No. 4,237,140, issued to J. R. Dudzinski on Dec. 2, 1980, describes an analgesic mixture of nalbuphine and acetaminophen. U.S. Pat. No. 4,282,215, issued to J. R. Dudzinski and W. K. Schmidt on Aug. 4, 1981, describes an analgesic mixture of nalbuphine and aspirin.
U.S. Pat. No. 3,161,654, issued to Shen on Dec. 15, 1964, discloses the synthesis of 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid, commonly called indomethacin: ##STR2## Winter et al., J. Pharmacol. Exp. Ther., 141, 369 (1963) disclose the pharmacological properties of indomethacin, and Winter and Flataker, J. Pharmacol. Exp. Ther., 150, 165 (1965) describe the analgesic properties of the compound.
U.S. Pat. No. 4,233,313 issued to J. F. Gardocki on Nov. 11, 1980 describes an analgesic mixture of indomethacin and acetaminophen.